While interleukin-8 was initially identified as a chemoattractant for neutrophils, and was known to bind a receptor on neutrophils.sup.8-10 it has in addition a wide range of pro-inflammatory activities including the stimulation of degranulation and the upregulation of the cell adhesion molecule MAC-1 and of the complement receptor CR1.sup.1. IL-8 can also mediate the inhibition of the adherence of neutrophils to activated endothelial cells.sup.2.
IL-8 is a member of a family of ten or more pro-inflammatory cytokines with an M.sub.r.sup.- 10,000.sup.1. This larger family of proteins is called the platelet factor 4 superfamily (Wolpe et al., "FASEB J."3:2565-73 [1989]). Some members of the platelet factor 4 superfamily, in general the subset referred to as CXC peptides (including IL-8), possess neutrophil agonist activity, e.g. NAP-2, MIP-2 and NAP-3 (MGSA/gro), and are referred to as "PF4A" herein.
It is an object of this invention to identify receptors for the pF4A family.
It is another object of this invention to obtain DNA encoding these receptors, and to express them in host cells.
It is an additional object of this invention to provide isolates of pF4A receptors for diagnostic and therapeutic purposes.
A still further object is to prepare variants of such receptors for therapeutic purposes or for purification of pF4A family members.
These and other objects of this invention will be apparent from the specification as a whole.